2008年1月31日 星期四

The Pharmaceutical Inspection Convention and Pharmaceutical Inspection Co-operation Scheme (PIC/S) are two international instruments between countries and pharmaceutical inspection authorities. The PIC/S is meant as an instrument to improve co-operation in the field of Good Manufacturing Practices between regulatory authorities and the pharmaceutical industry.

The PIC (Pharmaceutical Inspection Convention) was founded in October 1970 by the European Free Trade Association (EFTA), under the title of "The Convention for the Mutual Recognition of Inspections in Respect of the Manufacture of Pharmaceutical Products". The initial members comprised the 10 member countries of EFTA at that time. In the early 1990s it was realized that because of an incompatibility between the Convention and European law, it was not possible for new countries to be admitted as members of PIC. European law did not permit individual EU countries that were members of PIC to sign agreements with other countries seeking to join PIC.

As a consequence the Pharmaceutical Inspection Co-operation Scheme was formed on 2 November 1995. The Pharmaceutical Inspection Co-operation Scheme is an informal agreement between health authorities instead of a formal treaty between countries.

PIC and the PIC Scheme, which operate together in parallel, are jointly referred to as PIC/S. PIC/S became operational in November 1995.

Tainted Drugs Linked to Maker of Abortion Pill

BEIJING — A huge state-owned Chinese pharmaceutical company that exports to dozens of countries, including the United States, is at the center of a nationwide drug scandal after nearly 200 Chinese cancer patients were paralyzed or otherwise harmed last summer by contaminated leukemia drugs.

Feng Weiying, in Shanghai, said the legs of her son, Zhang Qingdong, 7, were paralyzed after he received injections from tainted batches of cancer drugs.

Chinese drug regulators have accused the manufacturer of the tainted drugs of a cover-up and have closed the factory that produced them. In December, China’s Food and Drug Administration said that the Shanghai police had begun a criminal investigation and that two officials, including the head of the plant, had been detained.

The drug maker, Shanghai Hualian, is the sole supplier to the United States of the abortion pill, mifepristone, known as RU-486. It is made at a factory different from the one that produced the tainted cancer drugs, about an hour’s drive away.

The United States Food and Drug Administration declined to answer questions about Shanghai Hualian, because of security concerns stemming from the sometimes violent opposition to abortion. But in a statement, the agency said the RU-486 plant had passed an F.D.A. inspection in May. “F.D.A. is not aware of any evidence to suggest the issue that occurred at the leukemia drug facility is linked in any way with the facility that manufactures the mifepristone,” the statement said.

When told of Shanghai Hualian’s troubles, Dr. Sidney M. Wolfe, a leading consumer advocate and frequent F.D.A. critic, said American regulators ought to be concerned because of accusations that serious health risks had been covered up there. “Every one of these plants should be immediately inspected,” he said.

The director of the Chinese F.D.A.’s drug safety control unit in Shanghai, Zhou Qun, said her agency had inspected the factory that produced mifepristone three times in recent months and found it in compliance. “It is natural to worry,” Ms. Zhou said, “but these two plants are in two different places and have different quality-assurance people.”

The investigation of the contaminated cancer drugs comes as China is trying to restore confidence in its tattered regulatory system. In the last two years, scores of people around the world have died after ingesting contaminated drugs and drug ingredients produced in China. Last year, China executed its top drug safety official for accepting bribes to approve drugs.

Shanghai Hualian is a division of one of China’s largest pharmaceutical companies, the Shanghai Pharmaceutical Group, which owns dozens of factories. Neither Shanghai Hualian nor its parent company would comment on the tainted medicine.

Last week, The New York Times asked the F.D.A. whether the Shanghai Pharmaceutical Group exported to the United States any drugs or pharmaceutical ingredients other than the abortion pill. But after repeated requests, the agency declined to provide that information; it did not cite a reason.

On at least two occasions in 2002, Shanghai Hualian had shipments of drugs stopped at the United States border, F.D.A. records show. One shipment was an unapproved antibiotic and the other a diuretic that had “false or misleading labeling.” Records also show that another unit of Shanghai Pharmaceutical Group has filed papers declaring its intention to sell at least five active pharmaceutical ingredients to manufacturers for sale in the United States.

One major pharmaceutical company, Pfizer, declined to buy drug ingredients from Shanghai Pharmaceutical Group because of quality-related issues, said Christopher Loder, a Pfizer spokesman. In 2006, Pfizer agreed to evaluate Shanghai Pharmaceutical Group’s “capabilities” as an ingredient supplier, but so far the company “has not met the standards required by Pfizer,” Mr. Loder said in a statement.

Because of opposition from the anti-abortion movement, the F.D.A. has never publicly identified the maker of the abortion pill for the American market. The pill was first manufactured in France, and since its approval by the F.D.A. in 2000 it has been distributed in the United States by Danco Laboratories. Danco, which does not list a street address on its Web site, did not return two telephone calls seeking comment.

Problems with the cancer drugs first surfaced last summer after leukemia patients received injections of one cancer drug, methotrexate. Afterward, patients experienced leg pain and, in some cases, paralysis. At the People’s Liberation Army No. 307 Hospital in Beijing, a 26-year-old patient, Miao Yuguang, was unable to stand up five days after being injected in the spine with the drug. “We were already unlucky to have this illness,” her father, Miao Futian, said of the leukemia. “Then we ran into this fake drug.”

The authorities recalled two batches of the drug, but issued only mild warnings because the cause of the problem was unclear. Officials with Shanghai Pharmaceutical Group stood by their products, saying that drug regulators investigating the plant had found no problems. But when another cancer drug made in the same factory — cytarabin hydrochloride — also began causing adverse reactions, investigators suspected contamination.

In September, health and drug officials announced that they had found that the two drugs were contaminated with vincristine sulfate, a third cancer drug, during production. After issuing a nationwide alert, the government announced a wider recall, and Shanghai’s drug agency sealed manufacturing units at the plant.

“Many people thought there was a problem with the hospitals,” said Zheng Qiang, director of the Center for Pharmaceutical Information and Engineering Research at Peking University. “It wasn’t until later that they discovered the problem was with the medicine.”

Chinese media attention on the case has surged, after a terse statement by China’s drug agency in December, accusing Hualian company officials of a systematic cover-up of violations at the facility that made the drugs.

Family members at the No. 307 hospital have counted 53 victims in Beijing, and say they were told that there were least 193 victims nationwide. It is unclear how many were paralyzed, because the authorities have not released an official figure. Relatives have joined to share information and advocate for the victims. Based on interviews with several families in Beijing and Shanghai, it appears that about half of those injected still cannot walk.

Wu Jianhua said his daughter, Wu Xi, 15, collapsed on her way to school after an injection in August. “We thought she was tired,” Mr. Wu said. Doctors now say she may never walk without a cane, he said.

Last week, on a window near the gate of the closed plant was a notice from the Shanghai Food and Drug Administration, dated Sept. 8, accusing the plant of “producing substandard medicine that poses major risks of causing serious harm to human health.” It identified a company official, Gu Yaoming, as the “person responsible” for the plant.

Records show Mr. Gu also met with the United States F.D.A. inspectors last May as part of the routine inspection of the plant that makes RU-486.

Reached by telephone, Mr. Gu declined to describe his role at the two plants. “I cannot answer your questions,” he said.

A spokeswoman for China’s Food and Drug Administration, Yan Jiangying, said that Shanghai Hualian had been stripped of its license to produce antitumor drugs, but that this action did not affect RU-486.

Hualian is the latest in a string of tainted medicine cases that have undermined confidence in the safety of drugs here. In 2006, at least 18 Chinese died after an intravenous drug used to treat liver disease, Armillarisin A, was laced with diethylene glycol, a toxic chemical used in some antifreeze. Also in 2006, at least 14 Chinese died after taking a Chinese antibiotic, Xinfu, which was not properly sterilized during production. And more than a hundred people died in Panama after taking cold medicine containing a mislabeled and toxic chemical from China.

In each of these cases, the manufacturer failed to follow good manufacturing practices to ensure the final product was safe.

Describing the cover-up at the factory, Ms. Zhou, the regulator who led the investigation, said workers did not tell investigators that vincristine sulfate — a drug too toxic for use in spinal injections — had been stored in a refrigerator with materials for other drugs.

“At the time, we didn’t think they had lied to us,” Ms. Zhou said. The deception sent investigators on a two-month hunt for other possible causes of the adverse reactions. “If they had been open about the vincristine sulfate in the beginning, maybe fewer people would have been harmed,” she added.

While regulators have accused factory employees of a systematic cover-up of violations in production, they have not said whether superiors at Shanghai Pharmaceutical were aware of it. “We’ll have to wait until the police investigation is finished” to make more details public, said Ms. Yan, the drug agency spokeswoman.

Mr. Zheng at Peking University said that producing multiple drugs in a single workshop was risky, but that some Chinese companies saw it as a way to save money. “It was an accident,” he said of the Hualian case. “But it was bound to happen.”

Jake Hooker reported from Beijing and Shanghai, and Walt Bogdanich from New York. Andrew Lehren contributed reporting from New York.

我們要評定領導者，除了考慮其不犯error of commission（因有所作為而犯錯，即做了不該做的，例如把共同因當特殊因處理等之），更要強調機會成本，即他不要犯太多 error of omission（因無為而犯錯，即有些事該做而卻未做），使得良機（新產品、新市場等之）喪失。

Error of CommissionAn error which occurs as a result of an action taken. Examples include when a drug is administered at the wrong time, in the wrong dosage, or using the wrong route; surgeries performed on the wrong side of the body; and transfusion errors involving blood cross-matched for another patient.

提供藥品服務(給病人用藥)的時間錯誤 或錯劑量 或路徑錯誤

開刀錯身體另一邊 輸錯交叉配血型之錯

能動失效

Active FailureAn error which is precipitated by the commission of errors and violations. These are difficult to anticipate and have an immediate adverse impact on safety by breaching, bypassing, or disabling existing defenses.

違反 回避 或使既有的防衛, 防御（物）而造成立即的安全問題作用

Error of OmissionAn error which occurs as a result of an action not taken, for example, when a delay in performing an indicated cesarean section results in a fetal death, when a nurse omits a dose of a medication that should be administered, or when a patient suicide is associated with a lapse in carrying out frequent patient checks in a psychiatric unit. Errors of omission may or may not lead to adverse outcomes. 顯示應剖腹生產可是因遲疑而造成胎死腹中

護士在該給病人服藥時卻忘掉了ㄅ或是在精神病院中因疏忽未能經常查訪病人而病人自殺

Sentinel Event Glossary of Terms

Accreditation WatchAn attribute of an organization's Joint Commission accreditation status. A health care organization is placed on Accreditation Watch when a reviewable sentinel event has occurred and has come to the Joint Commission's attention, and a thorough and credible root cause analysis of the sentinel event and action plan have not been completed within a specified time frame.

Action PlanThe product of the root cause analysis which identifies the strategies that an organization intends to implement to reduce the risk of similar events occurring in the future. The plan should address responsibility for implementation, oversight, pilot testing as appropriate, time lines, and strategies for measuring the effectiveness of the actions.

Active FailureAn error which is precipitated by the commission of errors and violations. These are difficult to anticipate and have an immediate adverse impact on safety by breaching, bypassing, or disabling existing defenses.

Adverse Drug Event (adverse drug error)Any incident in which the use of a medication (drug or biologic) at any dose, a medical device, or a special nutritional product (for example, dietary supplement, infant formula, medical food) may have resulted in an adverse outcome in a patient.

Adverse Drug Reaction (ADR)An undesirable response associated with use of a drug that either compromises therapeutic efficacy, enhances toxicity, or both.

Adverse EventAn untoward, undesirable, and usually unanticipated event, such as death of a patient, an employee, or a visitor in a health care organization. Incidents such as patient falls or improper administration of medications are also considered adverse events even if there is no permanent effect on the patient.

Aggregate DataData collected and reported by organizations as a sum or total over a given time period, for example, monthly or quarterly.

Barrier AnalysisThe study of the safeguards that can prevent or mitigate (or could have prevented or mitigated) an unwanted event or occurrence. It offers a structured way to visualize the events related to system failure or the creation of a problem.

BenchmarkingContinuous measurement of a process, product, or service compared to those of the toughest competitor, to those considered industry leaders, or to similar activities in the organization in order to find and implement ways to improve it. This is one of the foundations of both total quality management and continuous quality improvement. Internal benchmarking occurs when similar processes within the same organization are compared. Competitive benchmarking occurs when an organization's processes are compared with best practices within the industry. Functional benchmarking refers to benchmarking a similar function or process, such as scheduling, in another industry.

CausationThe act by which an effect is produced. In epidemiology, the doctrine of causation is used to relate certain factors (predisposing, enabling, precipitating, or reinforcing factors) to disease occurrence. The doctrine of causation is also important in the fields of negligence and criminal law. Synonym: causality.

Change AnalysisA study of the differences between the expected and actual performance of a process. Change analysis involves determining the root cause of an event by examining the effects of change and identifying causes.

Circadian RhythmThe rhythmic repetition of certain phenomena in living organisms at about the same time each day. Without cues provided by light, the human circadian cycle lasts 25.9 hours.

Clinical PathwayA treatment regime, agreed upon by consensus, that includes all the elements of care, regardless of the effect on patient outcomes. It is a broader look at care and may include tests and x-rays that do not affect patient recovery. Synonym: clinical path.

Common-Cause VariationSee variation.

ComplicationA detrimental patient condition that arises during the process of providing health care, regardless of the setting in which the care is provided. For instance, perforation, hemorrhage, bacteremia, and adverse reactions to medication (particularly in the elderly) are four complications of colonoscopy and its associated anesthesia and sedation. A complication may prolong an inpatient's length of stay or lead to other undesirable outcomes.

Coupled SystemA system which links two or more activities so that one process is dependent on another for completion. A system can be loosely or tightly coupled.

Error of CommissionAn error which occurs as a result of an action taken. Examples include when a drug is administered at the wrong time, in the wrong dosage, or using the wrong route; surgeries performed on the wrong side of the body; and transfusion errors involving blood cross-matched for another patient.

Error of OmissionAn error which occurs as a result of an action not taken, for example, when a delay in performing an indicated cesarean section results in a fetal death, when a nurse omits a dose of a medication that should be administered, or when a patient suicide is associated with a lapse in carrying out frequent patient checks in a psychiatric unit. Errors of omission may or may not lead to adverse outcomes.

Fault Tree AnalysisA systematic way of prospectively examining a design for possible ways in which failure can occur. The analysis considers the possible direct proximate causes that could lead to the event and seeks their origins. Once this is accomplished, ways to avoid these origins and causes must be identified.

Flow ChartA pictorial summary that shows with symbols and words the steps, sequence, and relationship of the various operations involved in the performance of a function or a process. Synonym: flow diagram.

FMECA (failure mode, effect, and criticality analysis)A systematic way of examining a design prospectively for possible ways in which failure can occur. It assumes that no matter how knowledgeable or careful people are, errors will occur in some situations and may even be likely to occur.

Iatrogenic 1Resulting from the professional activities of physicians, or, more broadly, from the activities of health professionals. Originally applied to disorders induced in the patient by autosuggestion based on a physician's examination, manner, or discussion, the term is currently applied to any undesirable condition in a patient occurring as the result of treatment by a physician (or other health professional), especially to infections acquired by the patient during the course of treatment. 2. Pertaining to an illness or injury resulting from a procedure, therapy, or other element of care.

Immediate CauseSee proximate cause.

Incident ReportThe documentation for any unusual problem, incident, or other situation that is likely to lead to undesirable effects or that varies from established policies and procedures or practices. Synonym: occurrence report.

Indicator 1A measure used to determine, over time, performance of functions, processes, and outcomes. 2. A statistical value that provides an indication of the condition or direction over time of performance of a defined process or achievement of a defined outcome.

Latent FailureAn error which is precipitated by a consequence of management and organizational processes and poses the greatest danger to complex systems. Latent failures cannot be foreseen but, if detected, they can be corrected before they contribute to mishaps.

Local TriggerAn intrinsic defect or atypical condition that can create failures.

MalpracticeImproper or unethical conduct or unreasonable lack of skill by a holder of a professional or official position; often applied to physicians, dentists, lawyers, and public officers to denote negligent or unskillful performance of duties when professional skills are obligatory. Malpractice is a cause of action for which damages are allowed.

NegligenceFailure to use such care as a reasonably prudent and careful person would use under similar circumstances.

Occurrence ScreeningA system for concurrent or retrospective identification of adverse patient occurrences (APOs) through medical chart-based review according to objective screening criteria. Examples of criteria include admission for adverse results of outpatient management, readmission for complications, incomplete management of problems on previous hospitalization, or unplanned removal, injury, or repair of an organ or structure during surgery. Criteria are used organizationwide or adapted for departmental or topic-specific screening. Occurrence screening identifies about 80% to 85% of APOs. It will miss APOs that are not identifiable from the medical record.

OutcomeThe result of the performance (or nonperformance) of a function(s) or process(es).

Pareto ChartA special form of vertical bar graph that displays information in such a way that priorities for process improvement can be established. It shows the relative importance of all the data and is used to direct efforts to the largest improvement opportunity by highlighting the "vital few" in contrast to the "many others."

ProcessA goal-directed, interrelated series of actions, events, mechanisms, or steps.

Proximate CauseAn act or omission that naturally and directly produces a consequence. It is the superficial or obvious cause for an occurrence. Treating only the "symptoms," or the proximate special cause, may lead to some short-term improvements, but will not prevent the variation from recurring.

Retrospective Review1. A method of determining medical necessity or appropriate billing practice for services that have already been rendered. 2. In behavioral health, evaluative activities conducted when an individual being served is no longer in active treatment.

Risk ContainmentImmediate actions taken to safeguard patients from a repetition of an unwanted occurrence. Actions may involve removing and sequestering drug stocks from pharmacy shelves and checking or replacing oxygen supplies or specific medical devices.

Risk ManagementClinical and administrative activities undertaken to identify, evaluate, and reduce the risk of injury to patients, staff, and visitors and the risk of loss to the organization itself.

Risk PointsSpecific points in a process that are susceptible to error or system breakdown. They generally result from a flaw in the initial process design, a high degree of dependence on communication, non-standardized processes, and failure or absence of backup.

Root CauseThe most fundamental reason for the failure or inefficiency of a process.

Root Cause AnalysisA process for identifying the basic or causal factor(s) that underlie variation in performance, including the occurrence or possible occurrence of a sentinel event.

Sentinel EventAn unexpected occurrence involving death or serious physical or psychological injury, or the risk thereof. Serious injury specifically includes loss of limb or function. The phrase, "or the risk thereof" includes any process variation for which a recurrence would carry a significant chance of a serious adverse outcome. Such events are called "sentinel" because they signal the need for immediate investigation and response.

Special-Cause VariationSee variation.

SurveillanceOngoing monitoring using methods distinguished by their practicability, uniformity, and rapidity, rather than by complete accuracy. The purpose of surveillance is to detect changes in trend or distribution to initiate investigative or control measures. Active surveillance is systematic and involves review of each case within a defined time frame. Passive surveillance is not systematic. Cases may be reported through written incident reports, verbal accounts, electronic transmission, or telephone hotlines, for example.

Underlying CauseThe systems or process cause that allow for the proximate cause of an event to occur. Underlying causes may involve special-cause variation, common-cause variation, or both.

VariationThe differences in results obtained in measuring the same phenomenon more than once. The sources of variation in a process over time can be grouped into two major classes: common causes and special causes. Excessive variation frequently leads to waste and loss, such as the occurrence of undesirable patient health outcomes and increased cost of health services. Common-cause variation, also called endogenous cause variation or systemic cause variation, in a process is due to the process itself and is produced by interactions of variables of that process is inherent in all processes, not a disturbance in the process. It can be removed only by making basic changes in the process. Special-cause variation, also called exogenous-cause variation or extrasystemic cause variation, in performance results from assignable causes. Special-cause variation is intermittent, unpredictable, and unstable. It is not inherently present in a system; rather, it arises from causes that are not part of the system as designed.

Which? is a subscription-only magazine and website run by Which? Ltd (formerly known as the Consumers' Association, which is still the official name of the charity). Based in the United Kingdom, it engages in advocacy campaigns on various consumer protection issues and aims to promote informed consumer choice in the purchase of goods and services, by testing products, highlighting inferior products or services, and raising awareness of consumer rights. It maintains its independence by not accepting advertising or freebies; everything bought for testing is paid for at full price. Which? is funded entirely by its subscribers and has no shareholders.

Which? carries out systematic testing of consumer products and financial services, the results of which are published in reports in the magazine. The Which? 'Best Buy' label is well-known and respected by industry and consumers. Tests are carried out on consumer items like electrical goods, cars, and computers, as well as health and financial services, and supermarkets. Testing highlights issues such as reliability and value-for-money.

The magazine also raises awareness of trading it believes goes against the interests of consumers. It offers advice on consumers' legal rights and reports on legal cases where it has fought for members' rights. In the May, 2003 issue, for example, the back page featured a couple who won compensation from their credit card firm after purchasing a poor holiday. Another case featured was a life assurance company which had not maintained customer records properly and was forced to pay compensation. Which? also communicates regularly with the OFT and recently brought a 'supercomplaint' against private dentists in the UK. However, Which? has been criticised for its use of junk mail prize draws, similar to Reader's Digest, to gain additional subscribers. It is moving away from this area[citation needed].

Which? Ltd produces several other specialist publications apart from the main Which? magazine. These include Holiday Which?, Computing Which? and Gardening Which. It also publishes several books including the annual Good Food Guide and Giving and Inheriting.

Jan. 25, 1945: Fluoridation — Better Teeth, or Commie Plot?

By Tony Long 01.25.08 | 12:00 AM

1945: Grand Rapids, Michigan, becomes the first U.S. city to fluoridate its drinking water supply.

Fluoridation, implemented as a means of reducing tooth decay, involves adding one part per million of fluoride to the water supply. (The optimum level, according to the Centers for Disease Control, falls between 0.7 and 1.2 ppm.) Fluorine, of which fluoride is a compound, is one of Earth's most abundant elements, found in almost everything. In mammals, the highest natural concentration of fluoride is found in bones and teeth.

Group Seeks New Warning About Botox

WASHINGTON — Botox and a similar injected drug have been associated with 16 deaths, four of them in children, and scores of serious injuries that occurred after the drug spread to vital organs, a health advocacy group says.

The drug, a neurotoxin that is used to relax muscles, should come with a far stronger warning label and patients should be given a letter detailing its risks, the group, Public Citizen, said in a petition filed Thursday with the Food and Drug Administration.

Julie Zawisza, a spokeswoman for the agency, said she could not comment while the petition was under review.

Executives at Allergan, the maker of Botox, issued a statement saying that adverse reactions were rare. And because many patients who get the drug are seriously ill, the company said, it is not proved that Botox caused the reactions. Solstice Neurosciences, the maker of a similar drug, Myobloc, did not return a message for comment.

Perhaps best known as a wrinkle remover, Botox is also approved to treat cervical dystonia, a painful knotting of neck muscles. Doctors inject it into multiple spots on the neck, relieving sometimes disabling pain for weeks or months.

But the injection sites sometimes come perilously close to the esophagus, causing partial paralysis that can lead patients to have difficulty swallowing and suffer aspiration pneumonia, caused by breathing in food or liquids, Public Citizen said.

Of the 16 people who died, only one is known to have been undergoing a cosmetic treatment for wrinkles. Most of the others suffered muscle problems or their condition was unknown.

The deaths might have been prevented had patients been adequately warned of the possible dangers, said Dr. Sidney M. Wolfe, director of Public Citizen’s health research group. The labels for Botox and Myobloc mention the issue but not prominently enough, Dr. Wolfe said.

“Nobody should die from the medical use of Botox,” Dr. Wolfe said. “The fact that they are shows that patients don’t have a clue about these problems.”

Health authorities in Europe have done a far better job of highlighting the drugs’ dangers, Dr. Wolfe said. The authorities in Britain and Germany have required drug manufacturers to send letters to doctors warning of the dangers.

On Aug. 9, the Danish Medicines Agency published an analysis of adverse events associated with the products. The analysis found 600 problems associated with the drugs, the petition stated. Half of the serious problems associated with the drugs occurred after the toxin spread, the petition said.

The drugs’ labels in Europe have a prominent section titled “special warnings and precautions for use” that warns of the dangers of the spread of the toxin. The Danish authorities also warned that muscle weakness associated with Botox may be long-lasting, especially among children, the elderly and those suffering serious neurological problems.

Patients in Europe also receive a leaflet warning them to seek medical help if they have trouble breathing, experience dry mouth or have trouble swallowing.

The drugs’ manufacturers and others have reported to the F.D.A. 658 cases of problems associated with Botox and Myobloc, Public Citizen said.

2008年1月22日 星期二

What That Cholesterol Trial Didn’t Show

The cholesterol drug Vytorin became known for its commercials showing people who look oddly similar to foods like tacos and banana cream pie. But now Vytorin is getting attention that is anything but funny.

Related

The medicine combines Zocor, a cholesterol-lowering statin, with Zetia, a drug that limits cholesterol’s absorption into the body, and the hope was that the combination would make it more effective than either drug standing alone. But last week Vytorin’s makers, Merck and Schering-Plough, announced that in a small study it had done no better than Zocor alone in slowing the growth of arterial plaque, which can lead to heart attacks. There’s nothing particularly alarming about the findings (unless you’re a shareholder, perhaps).

But the news set off a panic among patients using cholesterol drugs. One doctor said he assigned a nurse full time to take the calls “and convince patients not to stop their medicine.” Another patient argued with his doctor, claiming the study showed that the drug doubled heart attack risk. (It didn’t; the study wasn’t designed to measure heart attacks.)

“I think this study is being interpreted wrong,” said Dr. Paul D. Thompson, director of cardiology at Hartford Hospital, who personally uses Zetia and (like most of the doctors quoted in this article) has consulted with makers of cholesterol drugs.

He pointed out that Vytorin users did experience a larger drop in cholesterol than the Zocor users. The disappointment was that the decline didn’t translate into a bigger benefit in arterial health. “It didn’t show harm,” Dr. Thompson said. “There were no more cardiac events, no more side effects. There was just no change.”

The fallout from the study was not limited to Vytorin. It has led to a whole new set of questions for scientists about cholesterol drugs. Is lowering LDL, the “bad” cholesterol, all that counts? Or must a drug also raise HDL, the “good” cholesterol, and fight inflammation?

Adding to the confusion, the Vytorin makers dragged their feet on releasing the results, issued the findings in a press release rather than a medical journal and made a lot of people mad.

“Failed trials are important,” said Dr. Steven Nissen, chairman of cardiovascular medicine at the Cleveland Clinic. “The reason the medical community is upset about the delay in reporting this is that we learn as much from a study that fails as we do from a study that succeeds. People are not happy that we didn’t learn about this sooner.”

Dr. Nissen, who says he donates his drug-consulting fees to charity and doesn’t take a tax deduction, added that the study raised interesting scientific questions about the differences in cholesterol drugs.

The most popular — the statins, including Lipitor and Zocor — reduce the amount of cholesterol produced by the liver. In some studies, statins have lowered heart attack risk by 30 percent or more in high-risk patients. Statins also raise HDL levels and have an anti-inflammatory effect. The problem is that statins, particularly at high doses, can have a number of side effects, including muscle pain.

Zetia has a smaller anti-LDL effect than statins, and little effect on HDL or inflammation. On the plus side, because it works primarily in the digestive tract, it potentially has fewer side effects.

Vytorin, by combining Zocor and Zetia, produces a bigger drop in cholesterol than either drug could do alone, and without a marked increase in side effects. The problem is that there are no long-term studies showing that using the drug translates into fewer heart attacks or strokes.

The latest study was a step in that direction. It didn’t set out to measure heart attacks or strokes, but it did look at whether Vytorin slowed plaque buildup on artery walls more than a statin alone.

It didn’t. While it’s been reported that the Vytorin users had more plaque than the Zocor users, that’s not a scientifically correct reading of the data: the difference between the two groups was not statistically significant.

Most important, perhaps, nothing about the trial undermines the settled wisdom about cholesterol and heart disease. The science still shows that lower cholesterol is better, however you achieve it.

“Every way in which we have lowered LDL in the past” has been shown to reduce heart attacks and strokes, said Peter Libby, chief of cardiovascular medicine at Brigham and Women’s Hospital in Boston, who has consulted with drug companies. “All of these different routes to lowering bad cholesterol are correlated with a clinical benefit.”

To be sure, not everyone agrees that drugs are the best way to achieve lower cholesterol. But the Vytorin disappointment doesn’t “mean the whole concept is wrong,” said Dr. Daniel J. Rader, director of the preventive cardiology and lipid clinic at the University of Pennsylvania School of Medicine, who has also consulted with drug companies. “I firmly believe lowering cholesterol is the most validated, most important way we can reduce our risk of heart disease and stroke. Get your LDL down, and the lower the better.”

In fact, the real lesson of the Vytorin confusion may be exactly what its makers have promoted.

“It actually does get back to what the Vytorin commercials show,” said Dr. Nieca Goldberg, medical director of the women’s heart program at New York University, who does not consult for cholesterol drug companies. “Cholesterol comes from what you eat and your family history. I always put in a plug for modifying your diet and exercise. It may not bring about as big of a reduction as medication does, but it helps.”

Cancer Data? Sorry, Can’t Have It

By ANDREW VICKERS

Published: January 22, 2008

Not long ago, I asked a respected cancer researcher if he could send me raw data from a trial he had recently published. He refused. Sharing data would make the study team members “uncomfortable,” he said, as I might use this to “cast doubt” on their results.

I’d heard this before: as a statistician who designs and analyzes cancer studies, I regularly ask other researchers to provide additional information or raw data. Sometimes I want to use the data to test out a new idea or method of statistical analysis. And knowing exactly what happened in past studies can help me design better research for the future. Occasionally, however, there are statistical analyses I could run that might make an immediate and important impact on the lives of cancer patients.

A few years back, a study was published showing that a certain drug could prevent one type of cancer. The problem was that the drug didn’t work very well and had some side effects, so almost no one used it. At the same time, a colleague showed that a protein found in the blood could predict which patients were at high risk for cancer. We put two and two together and realized that we could use the protein test to work out which patients would benefit from the drug.

To make things even easier for us, it turned out that the researchers who had conducted the trial had actually measured this protein in all their patients. So we wrote to them and asked whether they would share their data. They refused on the grounds that they might consider a similar analysis at some point in the future. But years have passed, no such analyses have been forthcoming and few patients are benefiting from what could be a very effective drug.

Given the enormous physical, emotional and financial toll of cancer, one might expect researchers to promote the free and open exchange of information. The patients who volunteer for cancer trials often suffer through painful procedures and harsh experimental treatments in the hope of hastening a cure. The data they provide ought to belong to all of us. Yet cancer researchers typically treat it as their personal property.

I’m sometimes told that sharing data would violate patient privacy — though changing names to codes is easy enough. Other requests are killed by red tape. When a colleague and I wanted to analyze the data from a completed breast cancer trial, merely getting permission to speak to the study’s organizing committee required a one-hour phone call with the scientist in charge of the agenda. Only after another one-hour call with the committee itself were we allowed to submit a formal proposal — to which we received no response.

Most refusals are more blunt. “I am not prepared to release the data at this point,” one researcher wrote me, even though he was a government employee and his trial, which had been published several years earlier, was federally financed.

Dr John Kirwan, a rheumatologist from the University of Bristol in England, has studied researchers’ attitudes on sharing data from clinical trials. He found that three-quarters of researchers he surveyed, as well as a major industry group, opposed making original trial data available. It is worth restating this finding: most scientists doing research on how best to help those in pain, or at risk of death, want to keep their data a secret.

Dr. Kirwan went on to ask his subjects why. Their reasons were entirely trivial: one cited the difficult of putting together a data set (wouldn’t this have to be done anyway in order to publish a paper?); another was concerned that the data might be analyzed using invalid methods (surely a judgment for the scientific community as a whole). This is something of a clue that the real issue here has more to do with status and career than with any loftier considerations. Scientists don’t want to be scooped by their own data, or have someone else challenge their conclusions with a new analysis.

Yet this is exactly what cancer patients need. They want new results to be published as quickly as possible and to encourage a robust debate on the merits of key research findings.

An acquaintance of mine was recently diagnosed with breast cancer, and it gives me some comfort to know that there are drugs she can take that will improve her chance of cure. We know that these drugs are of benefit because more than 20 years ago, a group of Oxford statisticians persuaded researchers around the world to pool data from their breast-cancer trials.

With the rise of the Internet, sharing data has become a simple matter. Geneticists, for example, publish their raw data on a central Web site. The data from medical trials are given freely by patients. They should insist that these belong to science as a whole.

Andrew Vickers is a biostatistician at Memorial Sloan-Kettering Cancer Center in New York.

High Mercury Levels Are Found in Tuna Sushi

Recent laboratory tests found so much mercury in tuna sushi from 20 Manhattan stores and restaurants that at most of them, a regular diet of six pieces a week would exceed the levels considered acceptable by the Environmental Protection Agency.

A long, irregularly shaped gland in vertebrates, lying behind the stomach, that secretes pancreatic juice into the duodenum 十二指腸 and insulin, glucagon高(增)血糖素, and somatostatin( 抑制劑?) into the bloodstream.

[Greek pankreas : pan-, pan- + kreas, flesh.]

pancreas

A gland in the abdomen with two functions: the endocrine pancreas (the islets of Langerhans) secretes the hormonesinsulin and glucagon; the exocrine pancreas secretes the pancreatic juice. Known by the butcher as sweetbread or gut sweetbread, as distinct from chest sweetbread which is thymus.